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I.  LOCAL  ANESTHETICS  CONTAINING 
A CARBOXYL  GROUP 

II.  ADDITION  REACTIONS  OF  ALLYL 
AMINE  AND  MERCURIC  SALTS 


BY 


NORMAN  ALBERT  HANSEN 


THESIS 


FOR  THE 

DEGREE  OF  BACHELOR  OF  SCIENCE 


IN 

CHEMISTRY 


COLLEGE  OF  LIBERAL  ARTS  AND  SCIENCES 


UNIVERSITY  OF  ILLINOIS 


1922 


UNIVERSITY  OF  ILLINOIS 


I 0 

H 193 

K> 


■Augus-t— 12- i9-S — 


THIS  IS  TO  CERTIFY  THAT  THE  THESIS  PREPARED  UNDER  MY  SUPERVISION  BY 

-NORMAN-  -ALBERT-  -HANSEN 

ENTITLED  J>---LQCAIl^NES.THE.TXGS--C.QNTAIN1NG.-^-GAEB0XYL-GR.QP£^ 

JE  3A_  __  -AHD  IT  I_QN_  _SEA  CX IUN  S.  _ QE  _ ALL_YL_  AMXNE.  _ AND_  -HER  GIIRI C _ _S  AL  IS.  * 

IS  APPROVED  BY  ME  AS  FULFILLING  THIS  PART  OF  THE  REQUIREMENTS  FOR  THE 
DEGREE  OF  _3ACHELOR-QP-SO.IENaS 


rr  i 


Digitized  by  the  Internet  Archive 
in  2015 


https://archive.org/details/localanestheticsOOhans 


ACKNOWLEDGMENT 


The  writer  expresses  his  sincere  thanks 
and  appreciation  to  Dr,  Roger  Adams  for  his 
suggestion  of  these  problems  and  for  the  in- 
terest and  assistance  rendered  during  the 
experimental  work. 


CONTENTS 


PART  I 


Page 

I.  INTRODUCTION 1 

II.  HISTORICAL  AND  THEORETICAL 1 

III.  EXPERIMENTAL 5 

1.  Preparation  of  g-Chloro-Aceto-Acetic  Ester 5 

2.  Preparation  of  g-Bromo-Aceto-Acetic  Ester 6 

3.  Condensation  of  Diethyl  Amine  with  g-Chloro- 6 

Aceto-Acetic  Ester 

4.  Preparation  of  Diethyl  Ester  of  Amido  Diacetic...  8 

Acid 

5.  Preparation  of  Ethyl  Ester  of  n- Allyl  Glycine....  8 

6.  Preparation  of  Ethyl  Ester  of  Methyl  Glycine 9 


PART  II 

I.  INTRODUCTION  AND  THEORETICAL 11 

II.  EXPERIMENTAL.  12 

1.  Addition  of  Allyl  Amine  and  Mercuric  Chloride...  12 

2.  Addition  of  Allyl  Amine  Hydrochloride  to 14 

Mercuric  Chloride 

3.  Addition  of  Allyl  Amine  to  Mercuric  Acetate 15 

4.  Preparation  of  Diethyl  Allyl  Amine 15 

5.  Addition  of  Diethyl  Allyl  Amine  and  Mercuric....  16 

Acetate 


.til 


BIBLIOGRAPHY 


17 


1 


PART  ONE 

I.  INTRODUCTION. 

The  synthesis  of  many  local  anesthetics  has  been  achieved  in 
recent  years  and  many  theories  have  been  advanced  to  explain  their 
physiological  activity.  This  research  was  begun  with  the  hope  that 
the  structure  of  the  particular  substituted  diakyl  amino  ester  of 
p-amino  benzoic  acid,  whose  preparation  was  attempted  would  yield 
further  information  upon  one  or  the  other  of  these  theories.  Also 
that  it  would  assist  in  the  prediction  of  anesthetic  or  mydriatic 
action  in  compounds  possessing  somewhat  similar  structure. 


II.  HISTORICAL  AND  THEORETICAL. 

Atropine  and  cocain  are  closely  related  in  chemical  structure 
and  in  physiological  action.  The  mydriatic  action  and  anesthetic 
action  of  this  type  of  compound  has  been  extensively  studied.  The 
synthesis  of  new  compounds  with  slight  variation  in  grouping  has 
been  carried  out  for  the  purpose  of  determining  more  definitely  just 
which  groups  are  responsible  for  the  various  physiological  proper- 
ties. 

Atropine  as  obtained  from  the  leaves  of  the  belladonna  plant  is 
an  ester  yielding  on  hydrolysis  tropine  and  racemic  tropic  acid. 

Its  constitution  has  been  definitely  determined  through  the  re- 
searches of  Ladenberg,  Willst^ltter1  and  others.  For  the  sake  of 


2 


better  comparison  of  the  various  compounds  discussed  the  following 
method  of  writing  the  formulae  will  be  adopted. 


ATROPINS 


CHsOH 


Cocain  has  been  the  most  generally  used  local  anesthetic  and  it 
has  been  definitely  proven  by  the  above  mentioned  workers  that  it 
is  a derivative  of  ecognine  which  in  turn  is  a carboxyllic  deriva- 
tive of  tropine  and  therefore  any  study  of  cocain  or  cocain  like 
substances  requires  also  some  study  of  tropine  compounds. 

Many  tropeines  have  been  prepared  and  their  physiological  action 
studied  and  it  was  found  that  the  tropeines  derived  from  benzene  and 
cinnamic  acid  were  without  mydriatic  action,  while  those  derived 
from  mandelic  and  atrolactinic  acid  did  possess  this  property.  Those 
that  were  mydriatics  all  had  a benzene  nucleus  and  an  OH  group  in 
the  side  chain  containing  the  -0-C=0  group.  This  was  thought  at 
first  to  be  essential  for  mydriatic  action  but  later  many  excep- 
tions were  found.  The  structure  of  cocain  as  finally  established 
is  as  follows:. 

0 


// 

c-och3 


Einhorn  thought  after  its  synthesis  that  the  ester  grouping  was 
responsible  for  the  anesthetic  action  and  mydriatic  properties.  This 
he  found  by  further  experiment  to  be  more  or  less  true  but  that  it 
was  an  extremely  variable  factor.  It  appeared  then  that  there  must 
be  some  relation  between  physiological  action  and  the  structure  of 
the  side  chain.  Attention  was  then  directed  toward  the  alkamino 
esters  of  benzoic  acid  and  later  toward  the  alkamino  esters  of 
p-amino  benzoic  acid. 

These  researches  have  yielded  compounds  of  varying  anesthetic 
power  and  toxicity.  Generally  of  less  or  equal  toxicity  but  pos- 
sessing higher  anesthetic  power  than  cocain  for  certain  kinds  of 
anesthesia.  This  fact  may  be  said  to  be  particularly  true  for  most 
of  the  compounds  of  the  procain  series,  having  the  following  general 
formula :- 


NH2- 


- C-O-CHa-CHa-fl-CJHe 


?2h6 


Dialkyl  amino  alkyl  compounds  are  prepared  by  the  interaction 

of  halogen  alkyl  dialkyl  amines  and  the  alkali  salts  of  the  type 
0 

R-fl-H-RiX  where  R and  Rx  are  H or  any  radical  and  X is  an  electro 
negative  group  such  as  -COOC2H5,  C0CH3,  C0C6H5,  CN  for  example 
aceto  acetic  ester,  malonic  ester,  cyan  acetic  ester,  succinyl  suc- 
cinic ester.  Or  alternately  they  may  be  prepared  from  the  halogen 

alkyl  derivatives  of  bodies  of  the  above  type  such  as  chloro  ethyl 

2 

acetate,  chloro  aceto  acetic  ester  and  alkyl  amines. 


The  compound  desired  in  this  Investigation  had  the  following 

9 

structure:-  / \ 0 CH2-C-CR^C2H5 

NH2 C-0-9-CH2-N^C2H5 


4 


from  which  it  is  seen  that  it  is  similar  to  the  procain  type  and 
also  similar  to  cocain  but  with  the  complex  tropine  ring  broken* 

It  was  expected  that  this  compound  would  show  both  anesthetic  and 
mydriatic  properties*  Its  preparation  was  attempted  through  the 
condensation  of  g-chloro  aceto  acetic  ester  with  diethyl  amine, 
changing  the  ketone  to  the  alcohol  by  means  of  Grignar&s  reaction, 
condensation  of  this  alcohol  with  p-nitro  benzoic  acid  and  then  re- 
duction of  the  nitro  group  to  an  amino  group*  Structurally  the 
steps  are  represented  as  follows 


CH3 

6=o  — 

CHo-COOR 


GHgCl 

9=0 

ch2-coor 


(CoH5)2NH 


CHs-N ( C2H5 ) 2 CH2-N(C2H6)2 

C=0  =-*■  R-C-OH 

CH2-C00R  Grignard  CH2-C00R 


NO. 


— \ P 

bc-o-9-c 

/ CH„ 


h2-coor 

ch2-n(c2h5)2 


NH. 


oh2-ooor 
c-o-9-ch2-n(c2h5)j 


CH, 


Lucius  and  Brdning  have  succeeded  in  making  a somewhat  similar 
compound  but  by  the  reverse  method,  i.e.,  starting  with  the  halogen 
alkyl  dialkyl  amine.  The  structure  of  the  compound  is:- 

^0  H COOR  .C2H5 

c-o-o-q-ch2-ch2-n^ 

CH3  p{  c2H5 

It  was  prepared  by  allowing  chloro  ethyl  diethyl  amine  to  react 
with  the  sodium  salt  of  aceto  acetic  ester.  The  ketone  arising  from 
this  reaction  was  reduced  with  sodium  amalgam  to  the  alcohol  and 
then  condensed  with  benzoyl  chloride.  The  compound  was  reported  to 
have  marked  anesthetic  properties3. 


5 


III.  EXPERIMENTAL. 

Preparation  of  g-Chloro-Aceto-Acetic  Ester • 

The  method  used  in  the  preparation  of  g-chloro-aceto-acetic 
ester  is  that  of  Hamel4.  One  atom  of  Mg.  for  two  moles  of  ethyl - 
chloro-acetate.  The  ethyl -chloro -acetate  was  added  slowly  in  order 
to  keep  the  reaction  from  becoming  violent.  The  addition  requires 
approximately  two  hours.  A small  amount  of  mercuric  chloride  is 
introduced  as  a catalyst.  According  to  Hamel  the  reaction  may  take 
place  in,  ether,  benzene,  or  chloroform.  It  was  found  that  ether  as 
the  solvent  yielded  the  best  results. 

When  benzene  was  used  as  the  solvent,  the  reaction  was  vigorous 
but  it  was  impossible  to  hydrolize  v/ith  water  due  to  the  formation 
of  an  emulsion,  very  difficult  to  separate.  Even  the  addition  of 
NH*  Cl  to  the  water  did  not  prevent  the  formation  of  Mg(0H)2. 

The  reaction  in  ether  solution  ran  smoothly  and  the  product 
hydrolyzed  by  pouring  it  into  ice  water  acidulated  with  acetic  acid. 

The  oily  layer  w as  separated  and  vacuum  distilled.  The  ester  dis- 

o 

tilled  at  110  at  25  mm.  From  a half  mole  run  10  gms.  of  ethyl- 

° , 

chloro-acetate  was  recovered,  the  yield  of  the  ester  was  30  / • 

The  index  of  refraction  was  found  to  be  1.4458.  Hamel  reported 
1.4545. 

The  use  of  redistilled  materials,  and  also  using  the  ethyl- 

chloro-acetate  recovered  in  previous  rims,  increased  the  yield  of 

° / ° / 

crude  product  to  47  /o.  Redistilled  the  yield  was  40  /o  of  theory. 


i 


6 


Hydrolyzing  by  means  of  ice  and  H2SO4  proved  to  be  the  best,  as  the 
solution  was  more  easily  handled. 

o 

Andranoff  reports  yields  of  55  / Q by  a somewhat  similar  method6  . 

o 

Hamel  reports  yields  of  56  /o  of  theory. 

Preparation  of  g-Bromo-Aceto-Acetic  Ester. 

One  mole  of  bromine  was  added  to  one  mole  of  aceto-acetic  ester, 

v 

O 

dissolved  in  carbon  disulphide  cooled  to  0 . It  was  poured  into 
water  after  the  addition  was  complete  and  allowed  to  stand  for  12 
hours.  After  separating  and  drying  with  CaCl2  the  product  was 

o O 0 

vacuum  distilled.  It  was  fractionated  at  80  , 125  , and  140  at 

o 

25  mm.  The  140  fraction  should  have  been  the  g-bromo-aceto-acetic 
ester.  The  yield  was  very  small  and  its  preparation  was  not  again 
attempted.  The  bromine  atom  enters  in  the  alpha  position  but  on 
standing  shifts  over  to  the  gamma  position6. 

Condensation  of  Diethyl  Amine  Y/ith 
g-Chloro-Aceto-Acetie  Ester. 

One  mole  of  g-chloro-aceto-acetic  ester  was  added  slowly  to  two 

o 

moles  of  diethyl  amine  dissolved  in  ether  and  cooled  to  0 . The 
hydrochloride  of  diethyl  amine  formed  during  the  reaction  was  fil- 
tered from  the  solution  and  the  condensation  product  then  precipi- 
tated. It  in  turn  was  filtered  and  it  was  spread  upon  filter  paper 
to  dry  thoroughly.  The  crystals  assumed  a pink  color  and  the  pro- 
duct was  then  placed  in  a bottle  and  stoppered.  An  intense  heat 
soon  developed  and  the  product  decomposed.  Diethyl  amine  hydro- 


7 


o o 

chloride  and  another  compound  whose  melting  point  was  128  -130  were 


isolated  from  the  charred  material.  The  reaction  proceeded  as  fol- 
lows : - 

/ 0 0 H ,0  0 

(C2Hs)2NH  + C1CH2-C-CH2-C-0C2H5  = ( C 2 H5 ) 2N- CHa - C - CH2 - c - oc  2 h5 


The  decomposition  product  is: 


r2 

ch2 

c=o 

CH2 

C00R 


C00R 

?H2 

c=o 

CHO 


Hs 


COOR 

L H 


-C 


— — ► o=c. 


c=o 


/ H 

COOR 


H. 


The  reaction  was  also  tried  at  room  t emperature  but  the  decom- 
position then  took  place  immediately.  Analysis  of  the  decomposition 
product  gave  the  following  percentages 


Sample  I .1301  gms. 

Weight  of  water  formed  .0837  gms 

Weight  of  C02  formed  .2686  gms 

/o  H2  = 7.14  /„ 


/.  c 


=56.3  /< 


Sample  II  .1806  gms. 

Weight  of  water  formed  .1083  gms 

Weight  of  C02  formed  .3813 

/o  H2  =6.66 


f 

/< 


Theory  Hydrogen 


= 57.17 

6.3°/0 

O 

56.2  / 


Carbon 


Preparation  of  the  Diethyl  Ester  of 
Araido  Diacetic  Acid* 


8 


The  hexamethylene  tetramine  and  NaCN  were  dissolved  in  water  and 

o 

then  cooled  to  0 . H2S04  was  then  slowly  dropped  into  the  mixture. 

After  standing  several  days  the  solution  was  extracted  with  ether 
hut  no  product  was  recovered.  The  method  in  the  literature  calls 
for  the  use  of  pure  HCN  but  the  attempt  was  made  here  to  form  the 
product  using  NaOH  and  HsSOa7. 


Reactions : 

(CH2)6N4  + 6HCN  CN-CHa-NH-CHa-CN 


G00C2H5 

ch2  g2h5oh 

NH  * — 

GOOC 2Hg 


COOH 

CH2 

NH  -=r-  Ba( OH) 2 

i 

?H2 

COOH 


The  Preparation  of  the  Ethyl  Ester 
of  n-Allyl  Glycine. 


The  method  of  preparation  attempted  was  that  iof  Alpern  and  Weiz- 
s 

man  . The  calculated  quantity  of  allyl  amine  was  slov/ly  added  to  a 

o 

dry  ether  solution  of  ethyl  chloro-acetate  cooled  to  0 . At  the  end 

o 

of  one  hour  33  /0  of  sodium  hydroxide  was  added  and  then  potassium 
carbonate  in  sufficient  quantity  to  make  the  aqueous  layer  syrupy. 
This  then  was  extracted  with  ether,  and  the  extract  dried  v/ith  an- 
hydrous potassium  carbonate.  According  to  Alpern  and  Weizman  the 

o o 

ester  should  boil  at  75  -80  at  15  mm.  pressure.  Working  at  25  mm. 
pressure,  no  product  was  isolated  which  would  correspond  to  the 


9 


o o 

above  mentioned  product*  A fraction  at  130  -140  was  made,  the  tem- 

O o 

perature  then  quickly  rose  to  165  -180  • A large  amount  of  residue 
always  remained  in  the  distilling  flask.  The  distillate  which  were 

clear  and  colorless  at  first,  turned  yellow  on  standing.  On  redisi 

o o 

tillation  the  130  -140  fraction  yielded  no  definitely  boiling  com- 
pound and  decomposition  occurred.  This  product  was  thought  to  be  an 
amide  but  it  did  not  yield  any  qualitative  tests  for  that  group. 

The  Preparation  of  the  Ethyl  Ester 

* 

of  Methyl  Glycine. 

This  compound  was  to  be  prepared  thro  the  esterification  of 

worked 

methyl  amino-aceto-nitrile . The  idea  being  also  if  that  n-allyl 
glycine  might  also  be  prepared  similarly  from  n-allyl  amino-aceto- 
nitrile  • 

The  method  used  for  the  preparation  of  methyl  amino-aceto-nitrile 

9 

was  essentially  the  same  as  Adams  and  Marvel  use  in  the  preparation 
of  methylene  amino-aceto-nitrile.  Methyl  amine  hydrochloride  was 
used  instead  of  ammonium  chloride. 

Relative  proportions  of  two  moles  of  formaldehyde  to  one  mole  of 
methyl  amine  hydrochloride  were  placed  in  a flask  fitted  with  a 

mechanical  stirrer.  A thermometer  was  placed  in  the  liquid,  the 

o 

stirrer  started  and  the  whole  cooled  to  0 . A concentrated  solution 
of  one  mole  of  NaCN  was  then  slowly  dropped  into  the  mixture.  When 
one  half  of  the  sodium  cyanide  was  run  in,  glacial  acetic  acid 
(380  cc.  for  molecular  proportions)  was  also  slowly  run  into  the 
solution  so  that  the  addition  of  acid  and  cyanide  were  complete  at 


10 

the  seme  time.  NaCl  separates  during  the  reaction,  the  nitrile 
formed  as  an  oily  layer.  The  solution  was  made  alkaline,  the  ni- 
trile separated  and  distilled  under  vacuum.  The  product  boiled  con- 

o 

stantly  at  152  at  20  mm.  According  to  the  literature  methyl  amino- 

o o 

aceto-nitrile  should  boil  at  50  -70  at  12  ram.  This  product  then 
could  not  be  the  nitrile  sought. 

Esterification  of  this  nitrile,  using  a dry  solution  of  HC1  in 

o 

absolute  alcohol  yielded  a product  melting  at  169  uncorrected. 

Analysis  of  this  ester  hydrochloride  for  N by  Kjeldahl  Method 
gave  the  following  results :- 


Sample  I .1190  gms • 

N/ 

22.6  cc.  of  /10  HC1 
N/ 

11.8  cc.  of  /10  NaOH  used  for  back  titration 

N. 

10.8  cc.  of  /10  HC1  neutralized  by  NH3 

°/o  N = 12.7 


Sample  II 


.1441  gms. 


N 

22.32  cc.  of  /lO  HOI 
N. 

9.56  cc.  of  / 10  NaOH  used  for  back  titration 


12.76  cc.  acid  neutralized  by  the  NH3 
°/o  N = 12.41 


No  further  investigation  of  this  compound  was  carried  out 


11 

V 

PART  TWO 

MERCURY  COMPOUNDS  OF  ALLYL  AMINE. 

I.  INTRODUCTION  AND  THEORETICAL. 

This  investigation  was  -undertaken  with  the  idea  in  view  of  de- 
termining whether  allyl  amine  formed  similar  mercury  compounds  to 
allyl  alcohol.  Considerable  work  has  been  done  upon  the  compounds 
of  allyl  alcohol  with  mercuric  salts10.  While  the  problem  is  still 
unsettled  the  probable  structure  of  these  products  has  been  narrowed 
down  to  two  classes  of  compounds,  the  propylene  glycol  mercuric 
salts  of  the  type  C H2 OH- C HOH- C H2 HgX  and  the  dipropylene  oxide  di- 
mercuric  salts  of  the  type 


XHgCH2-CH-CH2 

6 6 

6h2(Jh  -CH2HgX 


The  formation  of  the  two  types  is  explained  by  assuming  that 
the  product  first  formed  is  the  simple  addition  of  HgX  and  -X  to 
the  double  bond  and  a hydrolysis  of  the  X radicle  in  an  alkaline 
solution  yielding  the  CH2OH-CHOH-CH2HgX  compound.  The  dipropylene 
oxide  dimercuric  salt  forms  in  an  acid  solution,  two  molecules  unit- 
ing with  the  elimination  of  two  molecules  of  HX. 


Upon  the  addition  of  allyl  amine  to  an  aqueous  solution  of 
H gCl2  an  insoluble  white  compound  is  precipitated.  Based  upon 
reasoning  similar  to  the  above  the  compound  might  possess  one  of 
the  following  formulae:- 


12 


HgCl  - GH2OH  - GHOH  - CH2NH2 


CH2  = CH  - CH2NH2HgCl2 


HgCl  - CH2  - CH  - CH2 


H - N N - H 


CH2-  CH  - CHgHgCl 


The  solution  of  this  problem  was  approached  as  follows: 

(1)  Attempt  to  replace  the  HgCl  group  with  iodine, 
reduction  of  the  iodine  compound,  with  the  sub- 
sequent formation  of  2,5  dimethyl  piperazine. 

(2)  Attempting  to  condense  the  mercury  compound 
with  p-nitro  benzoyl  chloride  or  benzoyl 
chloride • 

During  this  research  the  anesthetic  properties  of  some  of  these 
probable  compounds  v/as  kept  in  mind.  If  water  soluble  to  a high 
enough  degree,  it  might  be  expected  that  they  would  also  exhibit 
decided  antiseptic  properties  without  increasing  the  toxicity  very 
much.  A compound  of  which  we  might  expect  these  combined  physiologi- 
cal properties  would  possess  the  following  structure 


Prom  which  it  is  seen  that  it  possesses  great  similarity  to  the 
procain  type  of  anesthetic. 

II.  EXPERIMENTAL. 

Allyl  Amine  and  Mercuric  Chloride. 

The  addition  of  allyl  amine  to  a solution  of  mercuric  chloride 


Hg  — 0 — C — CH3 


13 


Is  followed  Immediately  by  the  precipitation  of  a white  compound 
virtually  insoluble  in  all  ordinary  solvents.  The  possible  struc- 
tures of  this  compound  are  as  follows: 


- H 

(1)  HgCl  - CH2  - C - CH2 

Hsl  I /$■ 

HC1—  N N — HG1 

I \ 

CH2  - C - CH2  - HgCl 

ft 


(2) 

ch2  = ch2  - 

NH2  - HgCl 2 

(3) 

HgCl  - CH2 

H 

- C - CH2  - nh2 

OH 

The  dihydrochloride,  represented  by  formula  (1)  seemed  the  most 
logical  but  attempts  to  free  the  base  through  treatment  with  NaOH, 
NH4OH  and  Na2COa  were  all  unsuccessful.  Upon  treatment  with  the 
calculated  amount  of  alkali  necessary  to  liberate  the  free  base, 
the  only  observable  result  was  a darkening  of  the  compound. 

Pyridine  was  tried  as  a solvent  and  the  compound  appeared  to  go 
Into  solution  very  easily.  Upon  filtering  and  diluting  with  water 
a white  crystalline  compound  was  precipitated.  This  new  compound 
did  not  redlssolve  in  pyridine  except  upon  the  addition  of  HC1#  It 
was  evident  then  that  these  two  compounds  were  not  identical.  The 

Q 

original  did  not  melt  while  the  second  melted  at  178  . Recrystal - 

O o 

lized  at  182  -185  • It  was  thought  that  possibly  the  alkalinity  of 
the  pyridine  had  been  sufficient  to  liberate  the  free  base  but  this 
idea  was  discarded  because  the  other  alkalis  had  no  such  action. 


Upon  treatment  of  the  second  compound  with  NaOH,  yellow  mercuric 


14 


oxide  precipitated  and  the  odor  of  pyridine  was  easily  noticeable. 
What  had  happened  was  that  pyridine  removed  not  the  HC1  group  but 
the  HgCl  groups  forming  either  C5HsNHgCl2  or  C6H5N  - HC1  - 2 HgCl2 , 

o o o 

melting  points  180  and  177  -178  respectively. 

Analysis  of  the  original  compound  for  mercury  did  not  indicate 
a great  deal  because  structures  represented  by  formulas  (1)  and  (2) 
have  identical  percentage  compositions. 

Hydrochloric  acid  decomposes  the  compound  again  into  allyl  amine 
and  mercuric  chloride,  upon  refluxing  for  a short  while. 

In  attempting  the  preparation  of  the  iodine  compound,  the  origi- 
nal material  was  ground  up  rather  finely,  suspended  in  water  and 
treated  with  KI.  The  yellow  Hgl  compound  was  formed  and  this  was 
treated  in  the  same  solution  with  the  calculated  amount  of  I.  A 
dark,  almost  black,  viscous  liquid  separates  upon  standing  and  this 
was  thought  to  be  iodine  compound. 

A zinc-hydrochloric  acid  reduction  of  this  compound  was  made 
without  success.  However,  the  amount  made  was  so  small  that  it  was 
impossible  to  investigate  it  thoroughly.  Working  with  larger  quan- 
tities would  yield  more  definite  information.  If  this  reduction  of 
the  iodine  compound  could  be  made  successfully,  2-5  dimethyl  pipera- 
zine would  be  formed  and  this  would  definitely  prove  the  ring  struc- 
ture of  the  compound. 

Addition  of  Allyl  Amine  Hydrochloride 
to  Mercuric  Chloride. 


Water  solutions  of  allyl  amine  hydrochloride  and  HgCl2  were 


15 


heated  slightly  until  the  reaction,  judged  by  entire  solution,  was 
complete.  The  solution  was  then  chilled,  when  a white  crystalline 

product  separated.  This  w as  filtered  and  recrystallized  from  butyl 

o 

alcohol  (m.  p.  158  ).  On  the  addition  of  alkali  to  a water  solution 
of  these  crystals,  yello w mercuric  oxide  precipitates. 

Addition  of  Mercuric  Acetate  to  Allyl  Amine. 

Allyl  amine  was  added  to  an  alkaline  solution  of  mercuric  acetate 
and  C02  passed  into  the  solution.  Upon  careful  evaporation,  a crys- 
talline product  remained  which  was  thought  to  have  the  following 
composition: 

CH3  - G - 0 - Hg  - CHg  - CH  - CH2  - NHS 

OH 

o o 

It  melted  at  59  -50  • NaOH  does  not  precipitate  HgO  and  the  com- 
pound is  easily  soluble  in  water. 

Condensation  with  p-nitro  benzoyl  chloride  was  attempted  with 
the  idea  of  preparing  an  anesthetic  of  the  type  mentioned  in  the 
introduction.  This  condensation  was  not  successful. 

The  Preparation  of  Diethyl  Allyl  Amine. 

One  molecular  part  of  allyl  bromide  was  slowly  dropped  into  two 
parts  of  diethyl  amine,  cooled  by  means  of  an  ice  salt  mixture.  The 

solution  was  made  alkaline  with  NaOH  when  the  amine  separated.  It 

O o 

was  then  distilled  and  the  fraction  between  110  -113  collected. 

This  is  pure  diethyl  allyl  amine  and  the  reaction  gives  almost  quan- 
titative yields. 


16 


Addition  of  Mercuric  Acetate  to 
Diethyl  Allyl  Amine, 

On  adding  diethyl  allyl  amine  to  a solution  of  mercuric  acetate, 
yellow  mercuric  oxide  is  precipitated  and  it  is  therefore  necessary 
to  add  enough  acetic  acid  to  keep  the  oxide  from  forming*  Upon 
evaporation  white  plate  like  crystals  separate  from  the  solution. 
These  crystals  do  not  melt  and  they  are  insoluble  in  ordinary  or- 
ganic solvents  and  water.  An  attempt  to  condense  this  compound  with 
p-nitro  benzoyl  chloride  was  also  unsuccessful. 


BIBLIOGRAPHY 


1.  May,  Synthetic  Drugs. 

2.  Chemical  and  Metallurgical  Engineering  25.,  25,  1064. 

3.  Centrall  blatt,  p.259,  July  27,  1921 

4.  Hamel.  Bulletin  Societe  de  Chimique  de  France  29.,  1921; 

Hamel.  Bulletin  Societe  de  Chimique  de  France  50,  1921. 

5.  Andranoff.  Berichte  46,  1021. 

6.  Berichte  25.,  2,  25;  Ann. 266,  77;  Cohen.  Organic  Chemistry, 

p.218. 

7.  Ann. 122  , 276;  278,  299. 

8.  Journal  of  the  Chemical  Society  £9,  84-87. 

9.  Adams  and  Marvel.  Organic  Chemical  Reagents.  1921. 

10.  Whitmore.  Organic  Compounds  of  Mercury,  p.131. 

11.  Ann. 134,  11  (1865). 


